Vascular Endothelial Growth Factor and Other Signaling Pathways in Developmental and Pathologic Angiogenesis

2004 ◽  
Vol 80 (1) ◽  
pp. 7-20 ◽  
Author(s):  
Gavin Thurston ◽  
Nicholas W. Gale
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Signaling Pathways ◽  
Vascular Endothelial ◽  
Endothelial Growth Factor

scholarly journals Pro-Angiogenic Effects of Resveratrol in Brain Endothelial Cells: Nitric Oxide-Mediated Regulation of Vascular Endothelial Growth Factor and Metalloproteinases

2012 ◽  
Vol 32 (5) ◽  
pp. 884-895 ◽  
Author(s):  
Fabricio Simão ◽  
Aline S Pagnussat ◽  
Ji Hae Seo ◽  
Deepti Navaratna ◽  
Wendy Leung ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Vascular Endothelial Growth Factor ◽  
Endothelial Cells ◽  
Growth Factor ◽  
Signaling Pathways ◽  
Tube Formation ◽  
Mitogen Activated Protein Kinase ◽  
Vascular Endothelial ◽  
Cerebral Endothelial Cells ◽  
Endothelial Growth Factor

Resveratrol may be a powerful way of protecting the brain against a wide variety of stress and injury. Recently, it has been proposed that resveratrol not only reduces brain injury but also promotes recovery after stroke. But the underlying mechanisms are unclear. Here, we tested the hypothesis that resveratrol promotes angiogenesis in cerebral endothelial cells and dissected the signaling pathways involved. Treatment of cerebral endothelial cells with resveratrol promoted proliferation, migration, and tube formation in Matrigel assays. Consistent with these pro-angiogenic responses, resveratrol altered endothelial morphology resulting in cytoskeletal rearrangements of β-catenin and VE-cadherin. These effects of resveratrol were accompanied by activation of phosphoinositide 3 kinase (PI3-K)/Akt and Mitogen-Activated Protein Kinase (MAPK)/ERK signaling pathways that led to endothelial nitric oxide synthase upregulation and increased nitric oxide (NO) levels. Subsequently, elevated NO signaling increased vascular endothelial growth factor and matrix metalloproteinase levels. Sequential blockade of these signaling steps prevented resveratrol-induced angiogenesis in cerebral endothelial cells. These findings provide a mechanistic basis for the potential use of resveratrol as a candidate therapy to promote angiogenesis and neurovascular recovery after stroke.

scholarly journals Vascular endothelial growth factor-A signaling in bone marrow-derived endothelial progenitor cells exposed to hypoxic stress

2013 ◽  
Vol 45 (21) ◽  
pp. 1021-1034 ◽  
Author(s):  
Brian R. Hoffmann ◽  
Jordan R. Wagner ◽  
Anthony R. Prisco ◽  
Agnieszka Janiak ◽  
Andrew S. Greene
Keyword(s):  
Bone Marrow ◽  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Signaling Pathways ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Tube Formation ◽  
Vascular Endothelial ◽  
Endothelial Progenitor ◽  
Endothelial Growth Factor

Bone marrow-derived endothelial progenitor cells (BM-EPCs) are stimulated by vascular endothelial growth factor-A (VEGF-A) and other potent proangiogenic factors. During angiogenesis, an increase in VEGF-A expression stimulates BM-EPCs to enhance endothelial tube formation and contribute to an increase in microvessel density. Hypoxia is known to produce an enhanced angiogenic response and heightened levels of VEGF-A have been seen in oxygen deprived epithelial and endothelial cells, yet the pathways for VEGF-A signaling in BM-EPCs have not been described. This study explores the influence of hypoxia on VEGF-A signaling in rat BM-EPCs utilizing a novel proteomic strategy to directly identify interacting downstream components of the combined VEGF receptor(s) signaling pathways, gene expression analysis, and functional phenotyping. VEGF-A signaling network analysis following liquid chromatographic separation and tandem mass spectrometry revealed proteins related to inositol/calcium signaling, nitric oxide signaling, cell survival, cell migration, and inflammatory responses. Alterations in BM-EPC expression of common angiogenic genes and tube formation in response to VEGF-A during hypoxia were measured and combined with the proteomic analysis to enhance and support the signaling pathways detected. BM-EPC tube formation assays in response to VEGF-A exhibited little tube formation; however, a cell projection/migratory phenotype supported the signaling data. Additionally, a novel assay measuring BM-EPC incorporation into preformed endothelial cell tubes indicated a significant increase of incorporated BM-EPCs after pretreatment with VEGF-A during hypoxia. This study verifies known VEGF-A pathway components and reveals several unidentified mechanisms of VEGF-A signaling in BM-EPCs during hypoxia that may be important for migration to sites of vascular regeneration.

scholarly journals Roles of Reactive Oxygen Species in Anticancer Therapy withSalvia miltiorrhiza Bunge

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Yu-Chiang Hung ◽  
Tai-Long Pan ◽  
Wen-Long Hu
Keyword(s):  
Reactive Oxygen Species ◽  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Protein Kinase ◽  
Cancer Cells ◽  
Signaling Pathways ◽  
Anticancer Therapy ◽  
Vascular Endothelial ◽  
Oxygen Species ◽  
Endothelial Growth Factor

Cancer is a leading cause of death worldwide. We aim to provide a systematic review about the roles of reactive oxygen species (ROS) in anticancer therapy withSalvia miltiorrhizaBunge (Danshen). Danshen, including its lipophilic and hydrophilic constituents, is potentially beneficial for treating various cancers. The mechanisms of ROS-related anticancer effects of Danshen vary depending on the specific type of cancer cells involved. Danshen may enhance TNF-α-induced apoptosis, upregulate caspase-3, caspase-8, caspase-9, endoplasmic reticulum stress, P21, P53, Bax/Bcl-2, DR5, and AMP-activated protein kinase, or activate the p38/JNK, mitogen-activated protein kinase, and FasL signaling pathways. Conversely, Danshen may downregulate human telomerase reverse transcriptase mRNA, telomerase, survivin, vascular endothelial growth factor/vascular endothelial growth factor receptor 2, CD31, NF-κB, Erk1/2, matrix metalloproteinases, microtubule assembly, and receptor tyrosine kinases including epidermal growth factor receptors, HER2, and P-glycoprotein and inhibit the PI3K/Akt/mTOR or estrogen receptor signaling pathways. Therefore, Danshen may inhibit cancer cells proliferation through antioxidation on tumor initiation and induce apoptosis or autophagy through ROS generation on tumor progression, tumor promotion, and tumor metastasis. Based on the available evidence regarding its anticancer properties, this review provides new insights for further anticancer research or clinical trials with Danshen.

Sign in / Sign up

Export Citation Format

Share Document